Chemotherapeutics kill tumor cells by interfering with various stages of the cell division process. There are a number of classes of chemotherapeutics including alkylating agents (e.g., cyclophosphamide, carmustine, cisplatin), antimetabolites (e.g., methotrexate, 5-FU, gemcitabine), cytotoxic antibiotics (e.g., doxorubicin, mitomycin) and plant derivatives (e.g., paclitaxel, vincristine, etoposide). Chemotherapy is used as a primary treatment for leukemias, other blood cancers, and inoperable or metastatic solid cancers.
However, current chemotherapeutic agents have a few problems, including limited efficacy, debilitating adverse side effects and development of multidrug resistance.
Novel piperazine compounds may provide potent new therapeutic molecules for the treatment of disorders such as tumors. In association with new development of an anti-tumor agent, U.S. Patent Application Publication No. 2003/0092910 presents the piperazine compounds having formula (A)

In U.S. Patent Application Publication No. 2003/0092910, the preparation of 1-[(2-alkoxyquinoxalin-3-yl)aminocarbonyl-4-arylpiperazine is presented wherein Ra and Rb are fused to form C3-C4 unsaturated ring. But the compounds of formula A have only hydrogen atom at C-5, C-6, C-7 and C-8 position of quinoxaline ring.
Namely, the compounds listed in U.S. Patent Application Publication No. 2003/0092910 has no other group except hydrogen at C-6 of quinoxaline ring of 1-[(2-alkoxyquinoxalin-3-yl)aminocarbonyl-4-arylpiperazine and the compounds with other groups except hydrogen at C-6 of quinoxaline have not been prepared and tested as an antitumor agent.
The present invention has studied 1-[(2-alkoxyquinoxalin-3-yl)aminocarbonyl-4-arylpiperazine derivatives because of its prominent antitumor activities with very low toxicities and presents novel 1-[(6,7-substituted alkoxyquinoxalinyl)aminocarbonyl]-4-(hetero)arylpiperazine derivatives with other functional groups except hydrogen at C-6 of quinoxaline ring of 1-[(2-alkoxyquinoxalin-3-yl)aminocarbonyl-4-arylpiperazine derivatives, the process of preparation and strong antitumor activities of these new compounds.
Accordingly, one object of the present invention is to provide the novel compounds, 1-[(6,7-substituted alkoxyquinoxalinyl)aminocarbonyl]-4-(hetero)arylpiperazine derivatives.
Another object of the present invention is to provide a process for the preparation of the novel compounds, 1-[(6,7-substituted alkoxyquinoxalinyl)aminocarbonyl]-4-(hetero)arylpiperazine derivatives.
A further object of the present invention is to use 1-[(6,7-substituted alkoxyquinoxalin-yl)aminocarbonyl]-4-(hetero)arylpiperazine derivatives as antitumor agent.